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CNVs conferring risk of autism or schizophrenia affect cognition in controls

Author

Listed:
  • Hreinn Stefansson

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Andreas Meyer-Lindenberg

    (Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany)

  • Stacy Steinberg

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Brynja Magnusdottir

    (Landspitali, National University Hospital, IS-101 Reykjavík, Iceland)

  • Katrin Morgen

    (Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany)

  • Sunna Arnarsdottir

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
    Landspitali, National University Hospital, IS-101 Reykjavík, Iceland)

  • Gyda Bjornsdottir

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • G. Bragi Walters

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Gudrun A. Jonsdottir

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Orla M. Doyle

    (Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK)

  • Heike Tost

    (Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany)

  • Oliver Grimm

    (Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany)

  • Solveig Kristjansdottir

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Heimir Snorrason

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Solveig R. Davidsdottir

    (Landspitali, National University Hospital, IS-101 Reykjavík, Iceland)

  • Larus J. Gudmundsson

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Gudbjorn F. Jonsson

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Berglind Stefansdottir

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

  • Isafold Helgadottir

    (Landspitali, National University Hospital, IS-101 Reykjavík, Iceland)

  • Magnus Haraldsson

    (Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
    University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland)

  • Birna Jonsdottir

    (Röntgen Domus, Egilsgötu 3, IS-101 Reykjavík, Iceland)

  • Johan H. Thygesen

    (Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark)

  • Adam J. Schwarz

    (Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940)

  • Michael Didriksen

    (H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark)

  • Tine B. Stensbøl

    (H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark)

  • Michael Brammer

    (Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK)

  • Shitij Kapur

    (Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK)

  • Jonas G. Halldorsson

    (University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland)

  • Stefan Hreidarsson

    (The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland)

  • Evald Saemundsen

    (University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland
    The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland)

  • Engilbert Sigurdsson

    (Landspitali, National University Hospital, IS-101 Reykjavík, Iceland
    University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland)

  • Kari Stefansson

    (deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland)

Abstract

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.

Suggested Citation

  • Hreinn Stefansson & Andreas Meyer-Lindenberg & Stacy Steinberg & Brynja Magnusdottir & Katrin Morgen & Sunna Arnarsdottir & Gyda Bjornsdottir & G. Bragi Walters & Gudrun A. Jonsdottir & Orla M. Doyle , 2014. "CNVs conferring risk of autism or schizophrenia affect cognition in controls," Nature, Nature, vol. 505(7483), pages 361-366, January.
    • Handle: RePEc:nat:nature:v:505:y:2014:i:7483:d:10.1038_nature12818
    DOI: 10.1038/nature12818
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    Cited by:

    1. Ralda Nehme & Olli Pietiläinen & Mykyta Artomov & Matthew Tegtmeyer & Vera Valakh & Leevi Lehtonen & Christina Bell & Tarjinder Singh & Aditi Trehan & John Sherwood & Danielle Manning & Emily Peirent , 2022. "The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Jonsdottir, Gudrun A. & Einarsson, Gudmundur & Thorleifsson, Gudmar & Magnusson, Sigurdur H. & Gunnarsson, Arni F. & Frigge, Michael L. & Gisladottir, Rosa S. & Unnsteinsdottir, Unnur & Gunnarsson, Bj, 2021. "Genetic propensities for verbal and spatial ability have opposite effects on body mass index and risk of schizophrenia," Intelligence, Elsevier, vol. 88(C).

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